Cyanate has been found to inhibit in vitro the sickling of erythrocytes from patients with sickle cell disease. This inhibition is a function of the amount of irreversible carbamylation of the NH2- terminal valine residue of hemoglobin S. The anti-sickling effect is retained when the cyanate-treated cells are returned to the patients. Although these preliminary results are hopeful, many aspects of this work must be expanded before cyanate can be developed into a useful therapeutic agent for the treatment of sickle cell disease. Clinical studies are now underway to determine its efficacy. Since cyanate is potentially a toxic drug, we propose to develop the following major areas: 1. Further study of cyanate inhibition of sickling in vitro. 2. The effect of blood with an increased oxygen affinity on the physiology of animals. 3. The effect of cyanate on the endocrine system. 4. The effect of long-term administration of cyanate to monkeys, mice and dogs. 5. The fate of cyanate in the body.